PDE2A p.Ile735=
c.2205C>T · rs392565 · VCV1167655
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 35.5%, sas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Pangolin | Δ0.21 | loss · gain 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -0.78 |
| Overall | ||
| CADD | 6.671 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
35.5%
South Asian · 32,177/90,670 alleles
Filtering AF
35.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 35%
Overall
29.7%
478,740/1,609,586 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 35.5% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 34.5% | 3 |
| Finnishnot grpmax-eligible | 31% | 3 |
| Remaining individualsnot grpmax-eligible | 29.9% | 3 |
| European (non-Finnish) | 29.7% | 3 |
| Middle Eastern | 29.5% | 3 |
| African / African-American | 26.9% | 4 |
| Amishnot grpmax-eligible | 26% | 4 |
| Admixed American | 25.8% | 4 |
| East Asian | 25.1% | 4 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PDE2A
- Protein
- p.Ile735=
- Coding
- c.2205C>T
- MANE Select
- NM_002599
- dbSNP
- rs392565
- Type
- single nucleotide variant
- Location
- chr11:72579585 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.17 · 44 PDB
- Residue 735
- a UniProt-annotated variant site (in iddpads); the pdease domain; an α-helix
Similar variants
- PDE2A c.1922+4C>T Uncertain significance ★★ same type
- PDE2A p.Ala157Val Uncertain significance ★★ ⚠ same type
- PDE2A p.Ala205Val Uncertain significance ★★ ⚠ same type
- PDE2A p.Ala349Thr Uncertain significance ★★ ⚠ same type
- PDE2A p.Arg226Cys Uncertain significance ★★ ⚠ same type
- PDE2A p.Arg790Gln Uncertain significance ★★ ⚠ same type
- PDE2A p.Asp34Glu Uncertain significance ★★ ⚠ same type
- PDE2A p.Asp59Asn Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pde2a-p-ile735 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown